{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:28:26Z","timestamp":1791221306378,"version":"4.1.0"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"20","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,5,19]]},"abstract":"<jats:p>\n                    In conventional \u03b1\u03b2 T cells, the Tec family tyrosine kinase Itk is required for signaling downstream of the T cell receptor (TCR). Itk also regulates \u03b1\u03b2 T cell development, lineage commitment, and effector function. A well established feature of\n                    <jats:italic>Itk<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice is their inability to generate T helper type 2 (Th2) responses that produce IL-4, IL-5, and IL-13; yet these mice have spontaneously elevated levels of serum IgE and increased numbers of germinal center B cells. Here we show that the source of this phenotype is \u03b3\u03b4 T cells, as normal IgE levels are observed in\n                    <jats:italic>Itk<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <jats:italic>Tcrd<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. When stimulated through the \u03b3\u03b4 TCR, Itk\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    \u03b3\u03b4 T cells produce high levels of Th2 cytokines, but diminished IFN\u03b3. In addition, activated Itk\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    \u03b3\u03b4 T cells up-regulate costimulatory molecules important for B cell help, suggesting that they may directly promote B cell activation and Ig class switching. Furthermore, we find that \u03b3\u03b4 T cells numbers are increased in\n                    <jats:italic>Itk<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, most notably the V\u03b31.1\n                    <jats:sup>+<\/jats:sup>\n                    V\u03b46.3\n                    <jats:sup>+<\/jats:sup>\n                    subset that represents the dominant population of \u03b3\u03b4 NKT cells.\n                    <jats:italic>Itk<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    \u03b3\u03b4 NKT cells also have increased expression of PLZF, a transcription factor required for \u03b1\u03b2 NKT cells, indicating a common molecular program between \u03b1\u03b2 and \u03b3\u03b4 NKT cell lineages. Together, these data indicate that Itk signaling regulates \u03b3\u03b4 T cell lineage development and effector function and is required to control IgE production in vivo.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0808459106","type":"journal-article","created":{"date-parts":[[2009,5,1]],"date-time":"2009-05-01T20:38:38Z","timestamp":1241210318000},"page":"8308-8313","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":116,"title":["Tec kinase Itk in \u03b3\u03b4T cells is pivotal for controlling IgE production in vivo"],"prefix":"10.1073","volume":"106","author":[{"given":"Martin","family":"Felices","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine C.","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Kosaka","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joonsoo","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie J.","family":"Berg","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,5,19]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.22.012703.104743"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2006.08.006"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.10.5056"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni734"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/07853890701449354"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.5.3007"},{"key":"e_1_3_3_7_2","doi-asserted-by":"crossref","first-page":"3030","DOI":"10.4049\/jimmunol.151.6.3030","article-title":"Development of T cell receptor-gamma delta cells. 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